Coronary microembolization induced myocardial contractile dysfunction and tumor necrosis factor-α mRNA expression partly inhibited by SB203580 through a p38 mitogen-activated protein kinase pathway / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>The microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused by the microinfarction induced by the microembolization may play an essential role. It is known that the activation of p38 mitogen-activated protein kinases (MAPK) in both infected and non-infected inflammation in myocardium may cause a contractile dysfunction. But the relation between the activation of p38 MAPK and microembolization is still unknown.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into three groups Sham group, coronary microembolization (CME) group and SB203580 group (n = 10 per group). CME rats were produced by injection of 42 µm microspheres into the left ventricle with occlusion of the ascending aorta. SB203580, a p38 MAPK inhibitor, was injected into the femoral vein after the injection of microspheres to make the SB203580 group. Left ventricular ejection fraction (LVEF) was determined by echocardiography. The protein concentration of P38 MAPK in the myocardium was assessed by Western blotting. The relative expression of mRNA for tumor necrosis factor (TNF)-α was assessed by the technique of semi-quantitative polymerase chain reaction amplification.</p><p><b>RESULTS</b>LVEF was depressed at three hours up to 12 hours in the CME group. Increased p38 MAPK activity and TNF-α mRNA expression were observed in the CME group. The administration of SB203580 partly inhibited p38 MAPK activity, but did not fully depress the TNF-α expression, and partly preserved cardiac contractile function.</p><p><b>CONCLUSIONS</b>p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly depress the TNF-α expression and preserve cardiac contractile function.</p>